Effects of local versus systemic administration of CXCR4 inhibitor AMD3100 on orthodontic tooth movement in rats

Abstract

Chemokines play pivotal roles in orthodontic tooth movement (OTM) through osteoclast-mediated bone resorption, but the underlying mechanism remains unclear. We aimed to elucidate the effects of serial local vs systemic administration of the chemokine receptor CXCR4 antagonist AMD3100 on OTM. The maxillary right first molar (M1) of rats was moved mesially using a 10 g of force nickel-titanium coil spring. The injections were performed every other day with phosphate-buffered saline as a control, whereas local and systemic animals were injected with AMD3100 at the buccal palatal mucosa adjacent to M1 and subcutaneously, respectively. OTM distance and alveolar bone were examined by microcomputed tomography and histologic analysis. Osteoclast numbers were quantified using TRAP staining. Cathepsin K and stromal cell-derived factor-1 (SDF-1) were evaluated using immunohistochemistry. Reverse transcriptase polymerase chain reaction for cathepsin K, Runx2, SDF-1, CXCR4, RANKL, and OPG were also examined. The results showed that OTM and osteoclast numbers were significantly decreased in the local and systemic groups compared with the control group, whereas there was no significant difference among the experimental groups. Local administration inhibited molar but not incisor movement. Trabecular thickness of the alveolar bone significantly increased in the systemic group compared with the control group, whereas local injection also affected bone quality in the same tendency as a systemic injection. AMD3100 significantly downregulated the mRNA expression levels of cathepsin K, Runx2, SDF-1, RANKL, and RANKL/OPG ratio in both experimental groups. In conclusion, local administration of AMD3100 can control initial OTM and diminish bone resorption processes during OTM via inhibition of the SDF-1/CXCR4 axis, similar to the systemic administration.